选择性COX-2抑制剂尼美舒利对大鼠乳腺癌的影响及机理研究

Effect of Nimesulide on DMBA-Induced Mammary Tumors in Rats

目的 研究选择性环氧合酶2(COX 2)抑制剂尼美舒利(nimesulide,NIM)对二甲基苯并蒽(DMBA)诱导的Wistar大鼠乳腺癌产生的影响,探讨其抗肿瘤机理。方法 将大鼠按随机数字表法分为致癌组、NIM组、饮食对照组及药物对照组,观察乳腺肿瘤发生的潜伏期、诱发率以及肿瘤的数目和体积。用TUNEL法和PCNA免疫组化法分别检测细胞凋亡和增殖指数。结果 NIM组大鼠乳腺肿瘤潜伏期比致癌组明显延长〔(115±14.8)d vs (84±15.6) d,P<0.01〕,肿瘤诱发率明显低于致癌组(46.4% vs 69.2%, P<0.05),肿瘤数目及体积明显少于致癌组〔(0.82±0.31)个vs (1.52±0.43)个,(3.24±1.21) cm3 vs (6.03±1.84) cm3,P<0.05〕; NIM组肿瘤细胞的增殖指数下降,凋亡指数明显增高,与致癌组相比差异有显著性意义〔(20.25±4.97)% vs (36.36±5.02)%,(42.54±13.24)% vs (18.14±6.66)%,P<0.05〕。结论 NIM通过抑制肿瘤细胞的增殖、诱导凋亡,降低了DMBA诱发的大鼠乳腺癌的发生率。

Objective To observe the effect of nimesulide (NIM) on DMBA-induced mammary tumors and to investigate possible mechanisms of inhibiting tumors. Methods The Wistar rats were randomly divided into four groups: DMBA group, NIM+DMBA group, NIM+diet group and diet group. The incidence and mean latent phase of mammary tumors were observed. The number and volume of tumors in every rat were measured. The apoptosis index and proliferation index were evaluated by TUNEL assay and PCNA immunohistochemical staining respectively.Results The latent phases of mammary tumors in NIM+DMBA group were strikingly longer than those in DBMA group 〔(115±14.8) d vs (84±15.6) d, P < 0.01〕. The incidence of mammary tumors was 69.2% in DMBA group, 46.4% in NIM+DMBA group. There was obviously decreased incidence in NIM+DMBA group ( P < 0.05). The number and the mean volume of mammary tumors in every rat in NIM+DMBA group were markedly less than DBMA group 〔(0.82±0.31) vs (1.52±0.43),(3.24±1.21) cm 3 vs (6.03±1.84) cm 3, P <0.05〕. The apoptosis index was obviously higher and the proliferation index was markedly lower in NIM+DMBA group compared with DMBA group〔(42.54±13.24)% vs (18.14±6.66)%, (20.25±4.97)% vs (36.36±5.02)%, P < 0.05〕. Conclusion NIM can inhibit the development of DMBA-induced mammary tumors by inhibiting proliferation and inducing apoptosis.